The pharmacokinetics and pharmacodynamics of nicotine, after single and repetitive doses, will be examined in healthy volunteers and patients with coronary heart disease; and as a function of urinary pH and of age. Diurnal variation in nicotine blood concentrations, heart rate and rhythm, electro-cardiographic (Q-T) intervals and urinary catecholamine excretion during daily smoking of medium and low nicotine cigarettes will be studied. The relationship between nicotine blood concentrations and cardiovascular effects and aversiveness of the experience during rapid smoking of low, medium and high nicotine tobacco cigarettes will be examined. Pharmacokinetic data will be used to predict the time course of nicotine in the body during habitual tobacco smoking and to design future experiments to further explore the role of nicotine in tobacco dependence. Pharmacologic response data will be used in combination with kinetic data to predict periods of maximal effect and high risk periods for adverse cardiovascular effects.